Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson's disease patients for the identification and validation of biomarkers for Parkinson's disease subtypes, progression and pathophysiology

Abstract

Background: Parkinson's Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology.

Methods/design: DUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included.

Discussion: DUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication.

Trial registration: NCT04180865; registered retrospectively, November 28th 2019.

Keywords: Biomarkers; Cognition; Gastrointestinal microbiome; Longitudinal studies; Microbiota; Neurodegenerative diseases; Neuropsychology; Observational study; Ophthalmology; Parkinson disease.

Fig. 1

Baseline recruitment and assessments from Q4 2017 to Q3 2020 of treatment-naïve de novo PD subjects through the collaborative network of PD treating neurologists Parkinson Platform Northern Netherlands (PPNN). 1. Study procedures start at home with 1a. the collection of a saliva sample for genetic screening; 1b. Assessments of gastrointestinal function and stool sample collection; 1c. questionnaire assessments. 2. Participants visit the University Medical Center Groningen (UMCG) on 2 days for 2a. a complete cognitive assessment; 2b. imaging; 2c. ophthalmological assessments; 2d. clinical assessments. * In a subset of participants, intestinal wall permeability will also be assessed using blood samples and a urinary excretion test. ** Hyposmia is also assessed using the Sniffin’ sticks. Source clipart: clipart-library.com